Using methodology developed in our group over the last several years. We have identified two novel minor variants of histone 2A. named H2A.X and H2A.Z. Using peptide gel analysis, we have shown that one of these, H2A.Z, is quite different in primary sequence and in modification from the other H2A's but at the same time H2A.Z is conserved much more than other H2A's during evolution. H2A.X and H2A.Z are synthesized through the cell cycle in mammalian cells while the major variants H2A.1 and H2A.2 are synthesized only in S phase. The identification of these histones has enabled us to separate histone synthesis into S phase histone synthesis and basal histone synthesis which occurs in G1 and G2 as well as in S. Basal histone synthesis and S phase histone synthesis have different sensitives to hydroxyurea; studies with other antitumor agents of the antimetabolite class are in progress. Histone metabolism during DNA repair is also being studied.